National Human Genome Research Institute

National Institutes of Health U.S. Department of Health and Human Services

Task Force Recommends Against Routine Testing for Genetic Risk of Breast or
Ovarian Cancer in the General Population

September 2005

Primary care physicians should not routinely refer all women for genetic counseling
and DNA testing to detect the presence of specific BRCA1 and BRCA2 gene mutations
that may be associated with breast or ovarian cancers, according to a new recommendation
from the U.S. Preventive Services Task Force. However, if a woman has certain
specific family history patterns that put her at risk for these gene mutations,
her primary care physician should suggest counseling and possible DNA testing.
This is the first time the Task Force has addressed the issue of genetic counseling
and DNA-based genetic testing for any disease. These recommendations, along
with a review of the supporting evidence, appeared in the September 6 issue
of Annals of Internal Medicine.

BRCA1 and BRCA2 are genes that help control normal cell growth. Women who inherit
specific changes or mutations in one or both of these genes have a greater risk
of developing breast and/or ovarian cancer, especially if their family members
have had one or both of these cancers. However, only a small number of women-about
2 percent-have the specific family history patterns that put them at risk
for BRCA mutations. In the general population, only about 1 in 300 to 1 in 500
women are believed to have these harmful genetic mutations. Even among women
with these mutations, not everyone will actually develop breast or ovarian cancer.

Women who are at an increased risk of inheriting the BRCA1 or BRCA2 gene mutations
include those of Ashkenazi (predominantly Eastern European) Jewish descent with
a first- or second-degree relative with breast or ovarian cancer. A first-degree
relative could be a mother, sister, or daughter; a second-degree relative might
be a grandmother or an aunt. Risk factors for women not of Ashkenazi Jewish
background include having specific family history patterns, for example, multiple
first- or second-degree relatives with breast and/or ovarian cancer. The level
of risk for these women is best determined by obtaining a detailed family history
and making use of standardized risk assessment tools.

Women who do not have a family history of either breast or ovarian cancer and
are unlikely to test positive for the mutations should not be referred for testing,
the Task Force emphasized, noting that there are potential harms involved in
genetic testing, including false-positive test results. The Task Force does
recommend that, starting at age 40, all women should be screened for breast
cancer using mammography. This recommendation can be found at
at Screening for Breast Cancer.

Testing entails risks. A woman who tests positive for BRCA1 and BRCA2 gene
mutations may choose to undergo a procedure such as a preventive mastectomy
or oophorectomy-removal of the breast or ovaries-which might be unnecessary
if a given mutation would not lead to cancer. Women who test positive for genetic
mutations may also be vulnerable to job or insurance discrimination. Federal
and state laws provide a degree of protection against discrimination on the
basis of genetic information, but concerns persist. In addition, the cost of
DNA testing for BRCA mutations can range from several hundred to several thousand
dollars, and insurance policies vary regarding coverage of genetic testing.

For those women whose specific family history puts them at risk for genetic
mutations and possibly cancer, counseling and BRCA testing may offer significant
benefits. "A woman who gains an understanding of the risk she faces may
feel less anxious and have a sense of better control of her future," said
Task Force Chair Ned Calonge, M.D., who is also Chief Medical Officer and State
Epidemiologist for the Colorado Department of Public Health and Information.
"If the DNA test result is positive, the patient and her physician should
take a shared decision making approach in deciding which preventive measures
are appropriate."

The Task Force found evidence in the scientific literature that women with
BRCA1 and BRCA2 mutations can reduce their risk of developing breast or ovarian
cancer by mastectomy or oophorectomy. Women may also choose to undergo intensive
screening by frequent clinical breast examinations and mammography or preventive
chemotherapy, but the benefits remain uncertain.

The Task Force, sponsored by the Agency for Healthcare Research and Quality,
is the leading independent panel of private-sector experts in prevention and
primary care and conducts rigorous, impartial assessments of the scientific
evidence for a broad range of preventive services. Its recommendations are considered
the gold standard for clinical preventive services.

The Task Force based its conclusions on a report from a research team led by
Heidi D. Nelson, M.D., M.P.H., at the Evidence-based Practice Center at Oregon
Health & Science University in Portland.

The Task Force uses letters to rate its recommendations according to the strength
of the evidence it has found and the amount of net benefit (the size of the
benefits minus the harms) a particular preventive service offers. Possible grades
are "A" (strongly recommends), "B" (recommends), "C"
(no recommendation for or against), "D" (recommends against), or "I"
(insufficient evidence to recommend for or against). The Task Force recommends
against routine referral for genetic counseling or BRCA testing for women whose
family history does not indicate an elevated risk as defined in the recommendation
and accompanying review (a "D" recommendation). The Task Force does
recommend that women whose family history indicates an increased likelihood
of harmful BRCA1 and BRCA2 mutations be referred for genetic counseling and
evaluation for BRCA testing (a "B" recommendation).